Influenza is a respiratory infection caused by influenza virus. Influenza-infected patients complain of not only respiratory symptoms such as rhinorrhea and coughing, but also strong systemic symptoms including hyperthermia, arthralgia and/or chilliness, which may lead to death especially among the elderly and young children. Influenza virus is an RNA virus having negative-strand RNA as its genome. Frequent mutations occur in the phenotype or genomic nucleotide sequences of influenza virus, and hence the influenza virus occasionally gives rise to inter-species infection. In recent years, avian and swine influenza viruses have been confirmed to infect humans, and there is a concern that infection of these viruses will spread widely.
Influenza virus has hemagglutinin (HA) and neuraminidase (NA) on its surface. Currently, it is known that there are 16 subtypes for HA and 9 subtypes for NA. Depending on the combination of these subtypes, the type of influenza virus (e.g., H1N1, H3N2, H5N1, H7N7) is identified.
In recent years, various studies have been conducted for the development of anti-influenza virus drugs. At present, Tamiflu is commonly used as an anti-influenza virus drug. However, this drug is intended to suppress virus multiplication by prevention of virus spreading, but not intended to kill the virus. Thus, this drug has a problem in that it must be taken during the early stage of infection.
Conventionally used anti-influenza drugs are designed to target a protein on the virus surface, including NA as mentioned above or M2. For example, Tamiflu (oseltamivir) and Relenza (zanamivir) are NA inhibitors and inhibit the release of virus particles from infected cells (Non-patent Documents 2-5). Likewise, amantadine targets the viral proton channel (M2 protein) and inhibits virus uncoating (Non-patent Document 1).
However, due to its high ability to mutate, as described above, influenza virus will cause a mutation in the protein targeted by the drugs and will thereby acquire drug resistance. In fact, influenza virus strains resistant to amantadine and oseltamivir have already appeared and become a problem on a global scale.
Since influenza virus RNA polymerase plays an important role in virus multiplication after infection in humans, it can be a target for anti-influenza virus drugs. However, its expression has not yet been succeeded on a large scale. Furthermore, the three-dimensional structure of a target protein is essential information for the development of anti-influenza virus drugs, but such information has not yet been provided so far.